Protein that slows ageing also protects against diabetes

Washington: MIT researchers have found that a protein that slows ageing in mice and other animals also protects against the ravages of a high-fat diet, including diabetes.

More than a decade ago, MIT biology professor Leonard Guarente discovered SIRT1’s longevity-boosting properties and has since explored its role in many different body tissues.

In his latest study, he looked at what happens when the SIRT1 protein is missing from adipose cells, which make up body fat.

When put on a high-fat diet, mice lacking the protein started to develop metabolic disorders, such as diabetes, much sooner than normal mice given a high-fat diet.

“We see them as being poised for metabolic dysfunction. You’ve removed one of the safeguards against metabolic decline, so if you now give them the trigger of a high-fat diet, they’re much more sensitive than the normal mouse,” said Guarente, the Novartis Professor of Biology at MIT.

The finding raises the possibility that drugs that enhance SIRT1 activity may help protect against obesity-linked diseases.

Guarente first discovered the effects of SIRT1 and other sirtuin proteins while studying yeast in the 1990s. Since then, these proteins have been shown to coordinate a variety of hormonal networks, regulatory proteins and other genes, helping to keep cells alive and healthy.

In recent years, Guarente and his colleagues have deleted the gene from organs such as brain and liver to pinpoint its effects more precisely. Their previous work has revealed that in the brain, SIRT1 protects against the neurodegeneration seen in Alzheimer’s, Huntington’s and Parkinson’s diseases.

SIRT1 is a protein that removes acetyl groups from other proteins, modifying their activity. The possible targets of this deacetylation are numerous, which is likely what gives SIRT1 its broad range of protective powers, Guarente said.

The researchers also found that as normal mice aged, they were more susceptible to the effects of a high-fat diet than younger mice, suggesting that they lose the protective effects of SIRT1 as they age.

Ageing is known to increase inflammation, so Guarente is now studying whether that age-related inflammation also provokes SIRT1 loss.

This research appeared in the latest print edition of the journal Cell Metabolism.